Zaccarelli Mauro, Tozzi Valerio, Lorenzini Patrizia, Trotta Maria P, Forbici Federica, Visco-Comandini Ubaldo, Gori Caterina, Narciso Pasquale, Perno Carlo F, Antinori Andrea
Clinical Department bLaboratory of Antiviral Drug Monitoring, National Institute of Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy.
AIDS. 2005 Jul 1;19(10):1081-9. doi: 10.1097/01.aids.0000174455.01369.ad.
To evaluate the effect of drug class-wide resistance (CWR) on survival in HIV-infected individuals who underwent genotypic resistance test after antiretroviral failure.
Observational, longitudinal cohort study.
HIV-infected individuals experiencing treatment failure were enrolled at first genotypic resistance test. End-points were death for any cause, AIDS-related death and AIDS-defining event/death. CWR was defined according to the International AIDS Society consensus. Survival analysis was performed with Cox's model.
Among 623 patients enrolled and followed for a median of 19 months (interquartile range, 12-29), Kaplan-Meier analyses for end-points at 48 months in patients with no CWR, one CWR, two CWR or three CWR were 8.9, 11.7, 13.4 and 27.1%, respectively, for death; 6.1, 9.9, 13.4 and 21.5%, respectively, for AIDS-related death; and 16.0, 17.7, 19.3 and 35.9%, respectively, for new AIDS event/death. In a multivariate Cox's model, higher HIV RNA level, previous AIDS and detection of three CWR (hazard ratio, 5.34; 95% confidence interval, 1.76-16.24) were all significantly associated with increased risk of death, while higher CD4 cell count and use of a new boosted protease inhibitor drug after identifying genotypic resistance were associated with reduced risk. Detection of three CWR was also significantly associated with higher risk of AIDS-related death and new AIDS event/death.
Even in the late era of highly effective antiretroviral treatments, detection of CWR, particularly if extended to all three drug classes is related to poorer clinical outcome and represents a risk-marker of disease progression and death.
评估药物类别广泛耐药（CWR）对接受抗逆转录病毒治疗失败后进行基因耐药检测的HIV感染者生存的影响。
观察性纵向队列研究。
在首次基因耐药检测时纳入经历治疗失败的HIV感染者。终点为任何原因导致的死亡、艾滋病相关死亡以及艾滋病定义事件/死亡。CWR根据国际艾滋病协会共识定义。采用Cox模型进行生存分析。
在纳入的623例患者中，中位随访19个月（四分位间距，12 - 29个月），无CWR、1种CWR、2种CWR或3种CWR患者在48个月时的Kaplan - Meier分析显示，任何原因导致的死亡分别为8.9%、11.7%、13.4%和27.1%；艾滋病相关死亡分别为6.1%、9.9%、13.4%和21.5%；新发艾滋病事件/死亡分别为16.0%、17.7%、19.3%和35.9%。在多变量Cox模型中，较高的HIV RNA水平、既往艾滋病史以及检测到3种CWR（风险比，5.34；95%置信区间，1.76 - 16.24）均与死亡风险增加显著相关，而较高的CD4细胞计数以及在确定基因耐药后使用新型增强型蛋白酶抑制剂药物与风险降低相关。检测到3种CWR也与艾滋病相关死亡以及新发艾滋病事件/死亡的较高风险显著相关。
即使在高效抗逆转录病毒治疗的后期，检测到CWR，尤其是如果扩展到所有三类药物，与较差的临床结局相关，并代表疾病进展和死亡的风险标志物。
